Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy.In this study,polyethylene glycol(PEG)-coated magnetic p...Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy.In this study,polyethylene glycol(PEG)-coated magnetic polymeric liposome(MPL)nanoparticles(NPs)assembled from octadecyl quatemized carboxymethyl chitosan(OQC),PEGylated OQC,cholesterol,and magnetic NPs,and functionalized with epithelial growth factor receptor(EGFR)peptide,were successfully prepared for in-vivo liver targeting.The two-step liver targeting strategy,based on both magnetic force and EGFR peptide conjugation,was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse.The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force,but could also diffuse into tumor cells as a result of EGFR targeting.In addition,paclitaxel(PTX)was incorporated into small EGFR-conjugated MPLs(102.0土0.7 nm),resulting in spherical particles with high drug encapsulation efficiency(>90%).The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels.In conclusion,PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.展开更多
In the present work, we aimed to develop alginate-coated chitosan nanoparticles for oral insulin delivery. The N-[（2-hydroxy- 3-trimethylammonium）propyl] chitosan chloride （HTCC） was synthesized, and the quatemize...In the present work, we aimed to develop alginate-coated chitosan nanoparticles for oral insulin delivery. The N-[（2-hydroxy- 3-trimethylammonium）propyl] chitosan chloride （HTCC） was synthesized, and the quatemized chitosan nanoparticles （HTCC-T NPs） were prepared by ionic gelation of HTCC using tripolyphosphate （TPP）. The alginate-coated quatemized chitosan nanoparticles （HTCC-A NPs） were prepared by coating HTCC-T NPs with alginate （ALG） solution under mild agitation. Particle size, zeta potential, surface morphology, drug loading and entrapment efficiency of HTCC-A NPs were characterized using Zeta-sizer, TEM and HPLC assays. It was found that HTCC-A NPs exhibited uniform spherical particles with the size of （322.2±8.5） nm and positive charges （14.1±0.6） mV. Our data showed that the release behavior of HTCC-A NPs was quite different from that of HTCC-T NPs （without ALG coating） when incubated with various medium at different pH values in vitro, suggesting that ALG coating over the HTCC-T NPs improved the release profile of insulin from the NPs for a successful oral delivery. The ALG coating could also improve the stability of insulin against enzymatic degradation. From circular dichroism spectrum, it was revealed that HTCC-A NPs were capable of maintaining the conformation of insulin. The relative pharmacological bioavailability of HTCC-A NPs was 8.0%±2.5% by intraduodenal administration. The HTCC-A NPs significantly increased （P〈0.05） the relative pharmacological availability （2.2 folds） compared with HTCC-T NPs after oral administration. HTCC-A NPs significantly enhanced the in vivo oral absorption of insulin and exhibited promising potentials for oral delivery.展开更多
基金the Research Program Foundation of the Department of Education of Fujian Province for Young Talents(No.JK2017021)the Training Program of Department of Health of Fujian Province for Young Talents(No.2017-ZQN-41).
文摘Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy.In this study,polyethylene glycol(PEG)-coated magnetic polymeric liposome(MPL)nanoparticles(NPs)assembled from octadecyl quatemized carboxymethyl chitosan(OQC),PEGylated OQC,cholesterol,and magnetic NPs,and functionalized with epithelial growth factor receptor(EGFR)peptide,were successfully prepared for in-vivo liver targeting.The two-step liver targeting strategy,based on both magnetic force and EGFR peptide conjugation,was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse.The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force,but could also diffuse into tumor cells as a result of EGFR targeting.In addition,paclitaxel(PTX)was incorporated into small EGFR-conjugated MPLs(102.0土0.7 nm),resulting in spherical particles with high drug encapsulation efficiency(>90%).The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels.In conclusion,PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.
基金NSFC projects(Grant No.81273455 and 81072597)grants from Ministry of Education(Grant No.NCET-11-0014 and BM U20110263)the funding support from State Key Laboratory of Long-acting and Targeting Drug Delivery System,LUYE PHARMA
文摘In the present work, we aimed to develop alginate-coated chitosan nanoparticles for oral insulin delivery. The N-[（2-hydroxy- 3-trimethylammonium）propyl] chitosan chloride （HTCC） was synthesized, and the quatemized chitosan nanoparticles （HTCC-T NPs） were prepared by ionic gelation of HTCC using tripolyphosphate （TPP）. The alginate-coated quatemized chitosan nanoparticles （HTCC-A NPs） were prepared by coating HTCC-T NPs with alginate （ALG） solution under mild agitation. Particle size, zeta potential, surface morphology, drug loading and entrapment efficiency of HTCC-A NPs were characterized using Zeta-sizer, TEM and HPLC assays. It was found that HTCC-A NPs exhibited uniform spherical particles with the size of （322.2±8.5） nm and positive charges （14.1±0.6） mV. Our data showed that the release behavior of HTCC-A NPs was quite different from that of HTCC-T NPs （without ALG coating） when incubated with various medium at different pH values in vitro, suggesting that ALG coating over the HTCC-T NPs improved the release profile of insulin from the NPs for a successful oral delivery. The ALG coating could also improve the stability of insulin against enzymatic degradation. From circular dichroism spectrum, it was revealed that HTCC-A NPs were capable of maintaining the conformation of insulin. The relative pharmacological bioavailability of HTCC-A NPs was 8.0%±2.5% by intraduodenal administration. The HTCC-A NPs significantly increased （P〈0.05） the relative pharmacological availability （2.2 folds） compared with HTCC-T NPs after oral administration. HTCC-A NPs significantly enhanced the in vivo oral absorption of insulin and exhibited promising potentials for oral delivery.
